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Sinapic Acid Reduces Oxidative Stress and Pyroptosis via Inhibition of BRD4 in Alcoholic Liver Disease

Alcoholic liver disease (ALD) is one of the main causes of death in chronic liver disease. Oxidative stress and pyroptosis are important factors leading to ALD. Bromodomain-containing protein 4 (BRD4) is a factor that we have confirmed to regulate ALD. As a phenolic acid compound, sinapic acid (SA)...

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Autores principales: Chu, Junyi, Yan, Ran, Wang, Sai, Li, Guoyang, Kang, Xiaohui, Hu, Yan, Lin, Musen, Shan, Wen, Zhao, Yan, Wang, Zhecheng, Sun, Ruimin, Yao, Jihong, Zhang, Ning
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8212038/
https://www.ncbi.nlm.nih.gov/pubmed/34149421
http://dx.doi.org/10.3389/fphar.2021.668708
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author Chu, Junyi
Yan, Ran
Wang, Sai
Li, Guoyang
Kang, Xiaohui
Hu, Yan
Lin, Musen
Shan, Wen
Zhao, Yan
Wang, Zhecheng
Sun, Ruimin
Yao, Jihong
Zhang, Ning
author_facet Chu, Junyi
Yan, Ran
Wang, Sai
Li, Guoyang
Kang, Xiaohui
Hu, Yan
Lin, Musen
Shan, Wen
Zhao, Yan
Wang, Zhecheng
Sun, Ruimin
Yao, Jihong
Zhang, Ning
author_sort Chu, Junyi
collection PubMed
description Alcoholic liver disease (ALD) is one of the main causes of death in chronic liver disease. Oxidative stress and pyroptosis are important factors leading to ALD. Bromodomain-containing protein 4 (BRD4) is a factor that we have confirmed to regulate ALD. As a phenolic acid compound, sinapic acid (SA) has significant effects in antioxidant, anti-inflammatory and liver protection. In this study, we explored whether SA regulates oxidative stress and pyroptosis through BRD4 to play a protective effect in ALD. Male C57BL/6 mice and AML-12 cells were used for experiments. We found that SA treatment largely abolished the up-regulation of BRD4 and key proteins of the canonical pyroptosis signalling in the liver of mice fed with alcohol, while conversely enhanced the antioxidant response. Consistantly, both SA pretreatment and BRD4 knockdown inhibited oxidative stress, pyroptosis, and liver cell damage in vitro. More importantly, the expression levels of BRD4 and pyroptosis indicators increased significantly in ALD patients. Molecule docking analysis revealed a potent binding of SA with BRD4. In conclusion, this study demonstrates that SA reduces ALD through BRD4, which is a valuable lead compound that prevents the ALD process.
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spelling pubmed-82120382021-06-19 Sinapic Acid Reduces Oxidative Stress and Pyroptosis via Inhibition of BRD4 in Alcoholic Liver Disease Chu, Junyi Yan, Ran Wang, Sai Li, Guoyang Kang, Xiaohui Hu, Yan Lin, Musen Shan, Wen Zhao, Yan Wang, Zhecheng Sun, Ruimin Yao, Jihong Zhang, Ning Front Pharmacol Pharmacology Alcoholic liver disease (ALD) is one of the main causes of death in chronic liver disease. Oxidative stress and pyroptosis are important factors leading to ALD. Bromodomain-containing protein 4 (BRD4) is a factor that we have confirmed to regulate ALD. As a phenolic acid compound, sinapic acid (SA) has significant effects in antioxidant, anti-inflammatory and liver protection. In this study, we explored whether SA regulates oxidative stress and pyroptosis through BRD4 to play a protective effect in ALD. Male C57BL/6 mice and AML-12 cells were used for experiments. We found that SA treatment largely abolished the up-regulation of BRD4 and key proteins of the canonical pyroptosis signalling in the liver of mice fed with alcohol, while conversely enhanced the antioxidant response. Consistantly, both SA pretreatment and BRD4 knockdown inhibited oxidative stress, pyroptosis, and liver cell damage in vitro. More importantly, the expression levels of BRD4 and pyroptosis indicators increased significantly in ALD patients. Molecule docking analysis revealed a potent binding of SA with BRD4. In conclusion, this study demonstrates that SA reduces ALD through BRD4, which is a valuable lead compound that prevents the ALD process. Frontiers Media S.A. 2021-06-04 /pmc/articles/PMC8212038/ /pubmed/34149421 http://dx.doi.org/10.3389/fphar.2021.668708 Text en Copyright © 2021 Chu, Yan, Wang, Li, Kang, Hu, Lin, Shan, Zhao, Wang, Sun, Yao and Zhang. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pharmacology
Chu, Junyi
Yan, Ran
Wang, Sai
Li, Guoyang
Kang, Xiaohui
Hu, Yan
Lin, Musen
Shan, Wen
Zhao, Yan
Wang, Zhecheng
Sun, Ruimin
Yao, Jihong
Zhang, Ning
Sinapic Acid Reduces Oxidative Stress and Pyroptosis via Inhibition of BRD4 in Alcoholic Liver Disease
title Sinapic Acid Reduces Oxidative Stress and Pyroptosis via Inhibition of BRD4 in Alcoholic Liver Disease
title_full Sinapic Acid Reduces Oxidative Stress and Pyroptosis via Inhibition of BRD4 in Alcoholic Liver Disease
title_fullStr Sinapic Acid Reduces Oxidative Stress and Pyroptosis via Inhibition of BRD4 in Alcoholic Liver Disease
title_full_unstemmed Sinapic Acid Reduces Oxidative Stress and Pyroptosis via Inhibition of BRD4 in Alcoholic Liver Disease
title_short Sinapic Acid Reduces Oxidative Stress and Pyroptosis via Inhibition of BRD4 in Alcoholic Liver Disease
title_sort sinapic acid reduces oxidative stress and pyroptosis via inhibition of brd4 in alcoholic liver disease
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8212038/
https://www.ncbi.nlm.nih.gov/pubmed/34149421
http://dx.doi.org/10.3389/fphar.2021.668708
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